The Study On The Imbalance Of Oxidants/Antioxidants In The Patients With Lung Cancer

Objects:The changes of oxidants and antioxidants in the activities,the expression of mRNA and protein were evaluated in 57 serum,113 lung tumor and 58 tumor-free lung tissues collected between the years 2006 and 2007 from 113 individuals with surgically resectable lung cancer.To elucidate the factors that have the effect on the imbalance of the oxidant and antioxidant system,to explore the mechanism that induce the imbalance,to consummate the mechanism of the onset,development and treatment of lung cancer.Methods:The activities of TAOC,TSOD,MnSOD,CuZnSOD,GPx,H2O2 and MDA were determined by chromometry.MnSOD,CuZnSOD mRNA and protein expression were evaluated by reverse transcription polymerase chain reaction and Western analysis in tumor,as well as corresponding control tissues.Resulst:1.The cha- racteristics of the oxidants and antioxidants in the patients with lung cancer were:①To compare with the controls,the activities of TAOC,TSOD,MnSOD and GPx were lower obviously in serum,CuZnSOD activity and H2O2,MDA were higher(p< 0.01).In the control serum MnSOD activity was negativly correlated to MDA, TAOC activity was positivly correlated to H2O2(p<0.01).In the patients'serum H2O2 had the correla- tion with the activities of CuZnSOD,MnSOD and TAOC.MDA was correlated to GPx activity(P<0.05 or 0.01).②To compare with the level of these indexes in the tumor- free tissues,the activities of TAOC, TSOD, CuZnSOD, GPx were higher, H2O2 and MDA were lower in the tumor tissues(p<0.01), the activity of MnSOD was similar be- tween the groups(p>0.05).In the tumor-free tissues H2O2 was correlated to the activi- ties of TSOD and MnSOD,MDA was correlated to the activities of GPx and MnSOD (p<0.05 or 0.01). In the tumor tissues the activities of TSOD,CuZnSOD,MnSOD,GPx and TAOC had the correlation with MDA, the activities of MnSOD and TAOC had the correlation with H2O2,TAOC activity was correlated to the activities of TSOD, CuZnSOD,MnSOD,GPx(p<0.05 or 0.01).2.The factors that had the effects on the imbalance of the oxidants and antioxidants in the patients with lung cancer were:①To compare with the group of the squamous cell carcinoma,the activities of TSOD and CuZnSOD were lower and H2O2 was higher in the serum of the group of adeno- carcinoma; while H2O2,MDA were higher in the tumor tissues of the group of adeno- carcinoma (p<0.05 or 0.01).②The activities of oxidants/antioxidants in the serum and tumor tissues were not correlated to the cell differentiation, serum CEA,CKH and CKL immunohistochemical staining (p>0.05).③There was no relation between the activities of oxidants/ antioxidants and the TNM stages in the serum(p>0.05).MnSOD activity in the tumor tissues of stageⅢ+Ⅳwas higher than that of stageⅠ+Ⅱ(p< 0.05).④The indexes of immunohistochemical staining:⑴To compared with the group of the negative CEA,GPx activity was lower in the serum and SOD activity was high- er in the tumor tissues of the group with the positive CEA (p<0.05).⑵MDA was higher in the serum of the group with positive P63 than that of the group with negative P63 (p<0.01).⑶The activities of CuZnSOD and MDA in the tumor tissues of the group with positive TTF-1 were higher than those of the group with negative TTF-1(p<0.05).⑤The mean values plus or minus standard deviation of the indexes in the control serum and tumor-free tissues were used as the dividing margin to discriminate the normal or the abnormal value.⑴The incidence of lower TSOD in the serum of the group of adenocarcinoma was 50%,the incidence of higher TSOD in the tumor tissues was 38%,which were higher than the incidence of the group of squa- mous cell carcinoma(p<0.05 or 0.01).The incidence of higher TSOD in the tumor ti- ssuees of the group of stageⅢ+Ⅳand positive TTF-1 was 38.3% and 51.7% separa- tly (p<0.01).There was closed relation between the pathohistology,TNM classification and abnormal ratio of TSOD in the tumor tissues by Logistic regression analysis(p< 0.05).⑵The incidence of higher CuZnSOD in the serum of the group of squamous cell carcinoma was 85.2%.The incidence of higher CuZnSOD in the tumor tissues of the group with positve TTF-1 was 51.7 %(p<0.05 or 0.01).⑶The incidence of higher Mn- SOD in the tumor tissues of the group of stageⅢ+Ⅳwas 25.5%(p< 0.01).⑷The incidence of higher GPx in the tumor tissues of the group of low differentiation was 100%, the incidence of higher GPx in the tumor tissues of positive CEA was 44.1% (p<0.01).⑸The incidence of higher H2O2 in the serum of the group of adenocar- cinoma and lower H2O2 in the tumor tissues was more than 40%, and the incidence of lower H2O2 in the tumor tissues of the group of squamous cell carcinoma was 66.7% (p< 0.01).⑹The incidence of lower MDA in the tumor tissues of the group of squam- ous cell carcinoma was 44.1%, the incidence of lower MDA in the tumor tissues of the group with negative CEA and TTF-1 was 52.2% and 50% separately (p<0.01). There was closed relation between the TTF-1 and abnormal ratio of MDA in the tum- or tissues(p<0.05).⑺There was no significant difference in the groups with abnormal incidence of TAOC in the serum and the tumor tissues.3.The results of the expression of MnSOD and CuZnSOD mRNA and protein in tumor and tumor-free tissues are that:①There was less MnSOD mRNA and protein in tumor than in tumor-free lung.There was more CuZnSOD mRNA and protein in tumor than in tumor-free lung tissue(p<0.01).②There was no relation between the expression of MnSOD,CuZnSOD mRNA and protein and the pathohistology,histology differentiation,TNM stages,CEA in the serum,immunohistological staining CKH,CKL,CEA,P63(p>0.05).MnSOD prot- ein expression in the group with positive TTF-1 was higher than that in the the group with negative TTF-1(p<0.05).The incidence of lower MnSOD mRNA was 94.1% in squamous cell carcinoma(p<0.01).The incidence of lower MnSOD protein was 36.4% in the low differentiation.(p<0.01).Conclusion:㈠The characteristics of the imbalance between the oxidants and antioxidants in the patients with lung cancer are included that:1.In the serum the levels of antioxidants are higher except CuZnSOD and the oxidants are lower.The lower activity of TSOD is companied with that of MnSOD. The activities of some antioxidants are correlated to the contents of oxidants.It can be concluded that the abnormal activities of antioxidants and the accumulation of oxid- ants are correlated to the onset and development of lung cancer.2.The activites of antioxidants are higher in tumor than in tumor-free lung except MnSOD,while the contents of oxidants are lower.The higher TSOD activity is companied with higher CuZnSOD activity.The activities of some antioxidants are correlated to the contents of oxidants. It can be concluded that antioxidants activities induced by many factors are higher in the tumor tissues,especial CuZnSOD activity,and are correlated to the onset and development of lung cancer.㈡The factors that have the relation with the im- balance of oxidants/antioxidants are included that:1.The cell type of pathology.To compared with the squamous cell carcinoma,the activities of TSOD and CuZnSOD in serum are lower,H2O2 is higher,while H2O2 and MDA are higher in the tumor tissues of the adenocarcinoma.2.TNM stage.The activity of MnSOD and the incidence of higher TSOD and MnSOD in the tumor tissues of stageⅢ+Ⅳis higher than that of stageⅠ+Ⅱ.These demonstrate the effect of MnSOD on the development of lung cancer3.Tumor markers.By immunohistochemical staining,GPx activity is higher in the serum of the patients with positive CEA,MDA content is higher in the serum of the patients with positive p63, CuZnSOD activity and MDA is higher in the tumor tissues of the patients with positive TTF-1 than that of the patients with negative TTF-1.These demonstrate that CEA,p63,TTF-1 may be the inducers of GPx, CuZnSOD and lipid peroxidants.㈢To compare with the levels of the indexes in the tumor-free tissues,the expression of MnSOD mRNA and protein is lower,the expression of CuZnSOD mRNA and protein is higher in the tumor tissues.The higher expression of CuZnSOD protein is coincident with the change of its activity.The incidence of the lower MnSOD mRNA expression in the tumor tissues of the squm- ous cell carcinoma is higer than that of the adenocarcinoma.The incidence of the lower MnSOD protein expression in the low differentiation is higher than that in the middle and high differentiation.It can be illustrated that the cell type of pathology can cause the different expression of MnSOD mRNA,the lower expression of MnSOD protein is correlated to the degree of the differentiation.